身材矮小女童364例细胞遗传学及遗传因素分析

目的探讨染色体异常和身高的多基因遗传因素在身材矮小女童中对矮小身材产生的作用。方法1.染色体分析:取患儿外周血1mL,接种于1640培养液中,培养72h,行外周血淋巴细胞G显带染色体核型分析;2.多基因遗传因素分析:根椐双亲的平均身高计算儿童的遗传身高(靶身高),分析靶身高的分布特点,比较靶身高与实际身高的一致性比例。结果364例中染色体异常83例(22.80%)。其中以45,XO和46,X,i(Xq)为主,二者占70%。靶身高分布左移,76例靶身高低于2个标准差(-2s),与实际身高一致性为20.88%。染色体异常者中7例靶身高低于-2s,与实际身高一致性为8.43%。结论染色体异常是女童身材矮小的一个重要原因,应加强对身材矮小女童的染色体检查。父母平均身高低是造成女童身材矮小的另一重要原因。     

Increasing genome instability in adrenocortical carcinoma progression with involvement of chromosomes 3, 9 and X at the adenoma stage

The investigation of chromosomal aberrations in adrenocortical tumours has been limited by the difficulties of applying classical cytogenetics to tumours with low levels of proliferation. We have therefore applied the technique of interphase cytogenetics to paraffin-embedded archival specimens of 14 adrenocortical adenomas and 13 carcinomas. Hybridizations were performed using centromere-specific probes to chromosomes 3, 4, 9, 17, 18 and X, which have been shown to be altered in other types of tumours. Chromosomal imbalance was defined on the basis of changes in both chromosome index (CI) and signal distribution (SD). Where only one of these was altered, this was classified as a tendency to gain or loss. On the basis of the analysis of optimal hybridizations, carcinomas showed gains in all chromosomes studied, five of nine showing gains in multiple chromosomes. Gains were most common in chromosomes 3, 9 and, in particular X, eight of 11 showing gain, and one a tendency to gain. Chromosomal gain was seen less commonly in adenomas, but again chromosomes 3, 9 and X were involved. Losses were infrequent, only one carcinoma showing loss of chromosome 18, and adenomas showing a tendency to loss of chromosomes 4 (two cases), 17 (one case) and 18 (two cases). Our data suggest that changes in chromosomes 3, 9 and X are early events in adrenocortical tumorigenesis, and that there is increasing chromosomal instability with tumour progression.     

Chromosomes and human neoplasms

Numerical and structural chromosome aberrations are frequently found in neoplastic cells. As demonstrated by the new chromosome banding techniques these aberrations are not random, but tend to show a specific occurrence. A model example is the leukemias where many cytogenetical investigations have been done to date. In leukemia chromosome analysis serves the following purposes: to identify a neoplastic process, to confirm and strengthen the hematological diagnosis, for the early diagnosis of transformation from a chronic leukemia into its blastic phase and for following up the clonal evolution of a leukemic cell line. In the discussion of chromosomes and neoplasms it must be mentioned that individuals demonstrating chromosomal instability and some trisomic patients show a greater tendency toward the development of a malignancy.Malignancy is primarily a cellular phenomenon caused by a disturbance in cellular regulation, whose fine events are not known. Therefore the exact role of the chromosomes in neoplastic processes cannot be stated. From experimental investigations it appears that the affected chromosomes carry cell growth regulating factors and also that a specific aberration is the result of the action of a specific agent.     

135例非单纯Ph染色体的慢性髓系白血病细胞遗传学分析

本研究探讨135例非单纯Ph染色体慢性髓系白血病（CML）的染色体检查结果并进行细胞遗传学分析：135例CML染色体均采用骨髓细胞直接法和／或短期培养法制备，应用R显带技术对其进行显带分析。结果表明：经染色体检测的1210例的CML中135例有非单纯Ph染色体异常。本组135例非单纯Ph染色体CML中，慢性期87例、加速期21例、急变期27例.87例慢性期患者中，14例伴简单变异易位，22例伴复杂变异易位，其余的伴其他染色体异常，其中伴8号染色体三体4例，伴双Ph4例，伴i（17）5例；在21例加速期患者中，伴8号染色体三体4例，伴双Ph4例，伴i（17）3例；在27例急变期患者中，2例伴简单变异易位，3例伴复杂变异易位，其余的伴其他染色体异常，其中伴8号染色体三体5例，伴双Ph5例，伴i（17）2例。本组常见额外染色体异常检出率高低依次为＋Ph、＋8、i（17）、-Y、＋19和＋21。本组有16例伴简单变异易位，25例伴复杂变异易位。结论：CML是起源于多能干细胞的恶性血液病．染色体核型分析对CML的诊断、预后、发病机制的探讨和治疗方案的选择都具有重要的价值。     

Towards unlimited colors for fluorescence in-situ hybridization (FISH)

We describe a FISH protocol that allows rehybridization of complex DNA probes up to four times to the same specimen. This strategy, which we termed ReFISH, opens a wide range of new applications to conventional band pass filter epifluorescence microscopy. These include M-FISH karyotyping and cross-species color banding that emulate multiplex probe sets labeled with up to 12 fluorochromes in sequential hybridizations to the same specimen. We designed a human 24-color karyotyping probe set in combination with a 29-color cross-species color banding probe set using gibbon painting probes. Applying the ReFISH principle, 53 painting probes on individual metaphases were discriminated. This allowed simultaneous screening for inter- and intrachromosomal rearrangements on normal human diploid cells, a HeLa derived cell line, and highly rearranged gibbon chromosomes. Furthermore, the present ReFISH experiments successfully combine 24-color FISH with laser scanning confocal microscopy to study the 3D organization of all 46 human chromosome territories in individual interphase cell nuclei.     

Molecular and cellular biology of prostate cancer

Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial neoplasia appears as early as the third decade and as many as 80% of 80 year old men have epithelial cells in their prostate that fit the morphological criteria for cancer, only about 10% of men will ever have the clinical disease and less than 3% will die from it. There have been no significant proven interventions which have altered the natural history of the disease since hormone down regulation was introduced in the 1940s and new research has been poorly supported. There is however an urgent need to develop new criteria to distinguish those patients with localised disease who will benefit from intervention from those that do not require it or who will have occult extra prostatic metastases. Similarly, there is an urgent need to develop new treatment for those in whom the disease is extra-prostatic and therefore incurable by conventional treatments. This review covers the latest developments in epidemiology, cellular and molecular biology including new areas such as ion channels in the field of prostate cancer.     

Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome

Acute myeloid leukaemia (AML) secondary to myelodysplastic syndrome (MDS) is characterized by poor prognosis, namely in older patients. The combination of fludarabine (F) with cytarabine (ARA‐C) ± G‐CSF was proven as effective in patients with poor risk AML. The efficacy and toxicity of a regimen including F + ARA‐C as sequential continuous infusion (CI‐FLA) in 64 untreated patients aged >60 years, in which AML arose after a previous MDS, was investigated. Median age was 67 years (61–81). In patients achieving CR, an additional course, followed by G‐CSF to mobilize CD34+ cells and subsequent autologous stem cell transplantation (ASCT) were programmed. Overall, 43 patients (67%) achieved complete remission (CR). There were 10 induction deaths (16%), while 11 patients (17%) were refractory to induction treatment. Thirty‐four patients (79% of remitters) were eligible for the consolidation and 30 were monitorized for the mobilization of CD34+ cells, collection being successful in 20 of them (67%). Median number of CD34+ cells/kg collected was 6.8 × 10E6. Thirteen patients (20% of the whole population) received ASCT. Median disease free survival (DFS) and overall survival (OS) were 10 and 9 months, respectively. Survival at 5 years is projected to 15%. The only parameter significantly related to either DFS duration or OS duration was unfavourable cytogenetics, which did significantly influence also CR achievement. CI‐FLA is effective in elderly patients with AML secondary to previously diagnosed MDS. Best results are achievable in the subgroup of patients with diploid karyotype. Copyright © 2010 John Wiley & Sons, Ltd.     

染色体异常在非霍奇金淋巴瘤临床应用中的价值

非霍奇金淋巴瘤（non—Hodgkin lymphoma，NHL）是一组来源不同、生物学特征各异的异质性疾病。大量研究表明，非霍奇金淋巴瘤患者常伴有特异性的染色体异常。随着分子生物学和细胞遗传学的发展，有关NHL染色体核型异常在NHL诊断、治疗乃至预后判断中的价值的研究取得了重大的进展。本文就NHL的常见的几种染色体异常和染色体异常的检测在临床应用中的价值做一综述，并重点讨论非霍奇金淋巴瘤的分子异常，它不仅是其分子特点，而且是预测其预后和治疗反应的指征。